Ectopic Cushing's Syndrome Due to Concurrent Corticotropin-Releasing Hormone (CRH) and Adrenocorticotropic Hormone (ACTH) Secreted by Malignant Gastrinoma

Abstract

Ectopic Cushing's syndrome due to various malignancies is not uncommon. However, a few cases of ectopic Cushing's syndrome caused by corticotropin-releasing hormone (CRH), or CRH with adrenocorticotropic hormone (ACTH) have been reported. A 28-year-old woman presented with acute upper gastrointestinal bleeding caused by an active ulcer, located atypically in the 2nd portion of duodenum. Further work-up revealed high gastrin levels and abdominal computed tomography (CT) scans showed a large pancreatic head mass with multiple liver metastases. The serum cortisol and ACTH levels were checked due to hypokalemia with metabolic alkalosis and recent amenorrhea. Cortisol and ACTH were both highly elevated with pituitary hyperplasia and elevated CRH. The existence of ectopic ACTH and CRH in the liver biopsy was also demonstrated immunohistochemically. Since an operation was not feasible, chemotherapy was conducted using paclitaxel and etoposide. These two drugs were chosen according to the IN VITRO chemotherapy response assay to maximize the treatment. This report demonstrates concurrent ACTH- and CRH-related ectopic Cushing's syndrome caused by malignant gastrinoma with multiple liver metastases that was treated with marginal success using a multidisciplinary medical approach.

The corticotropin releasing factor system in cancer: expression and pathophysiological implications

“…However, these studies need to be confirmed using peptide-specific antibodies that discriminate between CRF and the homologue urocortins. In a later study, a 28-year-old woman, described with upper gastrointestinal bleeding caused by an active ulcer, a pancreatic head mass, and multiple liver metastases, was found to have a CRF-positive liver biopsy by immunohistochemical analysis [70].…”

Cushing’s Syndrome Due to CRH and ACTH Co-secreting Pancreatic Tumor—Presentation of a New Case Focusing on Diagnostic Pitfalls

“…A recently published study in children and adolescents reported that, in 3 out of 7 patients with ectopic ACTH/CRH syndrome, the primary tumor was located in the pancreas [6]. In adults, apart from pNET, ACTH/CRH co-secretion is described in thymic and bronchial carcinoids, pheochromocytomas, medullary thyroid cancer, and lung cancer [2,4,5,[7][8][9][10][11].…”

“…In 1993, Saeger et al described the first case of an islet cell carcinoma in which ACTH along with CRH secretion was present [4], following which another two cases of pNETs co-secreting ACTH and CRH were reported [2,5]. A recently published study in children and adolescents reported that, in 3 out of 7 patients with ectopic ACTH/CRH syndrome, the primary tumor was located in the pancreas [6].…”

Two Cases With Cushing Syndrome: What an Anesthesiologist Should Know

“…There are reports in literature on the concurrent CS and pheochromocytoma [3,4], sarcoidosis [5], pancreatic acinar cell carcinoma [6], pre-eclamptic findings [7], malignant gastrinoma [8], bronchial carcinoid lung tumor [9], pancreatic neuroendocrine tumor [10], Hippel-Lindau disease [10], or mesenteric neuroendocrine carcinoma [11]. Our patients had nothing of these associations.…”